Efficacy Regarding Renal Function of Everolimus in Combination With Specific Standard Immunosuppressive Regimen Lung Transplant Recipients

Lung Transplantation Clinical Trial

— 4EVERLUNG  

Official title:

A 2-arm, Prospective, Randomized, Controlled, Open-label, 12 Month Phase III Trial to Evaluate the Efficacy Regarding Renal Function of Everolimus in Combination With a Centre Specific Standard Immunosuppressive Regimen Consisting of CNI, Purinantagonists and Steroids Versus a Standard Triple Immunosuppressive Regimen in Lung Transplant Recipients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01404325
• Other study ID #: CRAD001ADE36
• Secondary ID: 2011-001539-21
• Status: Completed
• Phase: Phase 3
• Start date: February 1, 2012
• Est. completion date: January 5, 2017

Study information

• Verified date: November 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial evaluated the efficacy of an everolimus-based quadruple low immunosuppressive regimen versus a standard immunosuppressive regimen concerning kidney function in lung transplant recipients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: January 5, 2017
• Est. primary completion date: January 5, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Adult recipients of de novo cadaveric lung transplants 3-18 months prior to enrollment

Exclusion criteria:

• Patients with thrombocytopenia (platelets <100,000/mm³), with an absolute neutrophil count of <1,500/mm³ or leucopenia (leucocytes <3000/mm³), with anemia with Hb < 8g/dl at time of screening

• Patients with uncontrolled hypercholesterolemia (> 350 mg/dL; > 9.1 mmol/L) or hypertriglyceridemia (> 750 mg/dL; > 8.5 mmol/L) at time of screening

• Patients with a history of malignancy of any organ system, treated or untreated, during the last five years, whether or not there is evidence of local recurrence or metastases, except squamous or basal cell carcinoma of the skin Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Lung Transplantation

Intervention

Drug:
• standard therapy
centre specific CNI-based triple drug immunosuppression
• Everolimus
quadruple immunosuppressive regimen consisting of everolimus, CNI, MPA and steroids

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Muenchen

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Calculated Glomerular Filtration Rate (cGFR) According to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at 12 Months	Calculated Glomerular Filtration Rate (cGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at 12 months The CKD-EPI equation, expressed as a single equation, is GFR = 141 × min(Scr/?, 1)a × max(Scr/?, 1)^-1.209 × 0.993Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, ? is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/? or 1, and max indicates the maximum of Scr/? or 1	Month 12
Secondary	Calculated Glomerular Filtration Rate (cGFR) According to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at Month 1, 3, 6, 9, 12	Calculated Glomerular Filtration Rate (cGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at Month 1, 3, 6, 9 and 12. The CKD-EPI equation, expressed as a single equation, is GFR = 141 × min(Scr/?, 1)a × max(Scr/?, 1)^-1.209 × 0.993Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, ? is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/? or 1, and max indicates the maximum of Scr/? or 1	Month 1, 3, 6, 9, 12
Secondary	Calculated Glomerular Filtration Rate (cGFR) According to Cystatin C-based Hoek's Formula at Month 1, 3, 6, 9, 12	Calculated Glomerular Filtration Rate (cGFR) according to Cystatin C-based Hoek's formula at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 1, 3, 6, 9, 12	Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 1, 3, 6, 9, 12 cGFR (in mL/min/1.73 m2) = 186.3*(C-1.154)*(A-0.203)*G*R where C = the serum concentration of creatinine (mg/dL), A = age (years), G = 0.742 when gender is female, otherwise G = 1, R = 1.21 when race is black, otherwise R = 1.	Month 1, 3, 6, 9, 12
Secondary	Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 1, 3, 6, 9, 12	Calculated Glomerular Filtration Rate (cGFR) according to Cockcroft-Gault at Month 1, 3, 6, 9, 12 For men: GFR=(140-Age) x Body weight (kg) / 72 x Serum Creatinine (mg/dl) For women: GFR=0.85 (140 -Age) x Body weight(kg)/ 72 x Serum Creatinine (mg/dl)	Month 1, 3, 6, 9, 12
Secondary	Incidence of Patients Experiencing a Decline in GFR of < 10, 10-15, 15-20, 20-25 and > 25 mL/Min From Baseline to Month 6 and 12.	Incidence of patients experiencing a decline in GFR of < 10, 10-15, 15-20, 20-25 and > 25 mL/min from Baseline to Month 6 and 12calculated by the CKD-EPI method. Participants are counted in each decline level observed for that participant; this means participants may be counted in more than 1 decline level.	Baseline, Month 6, Month 12
Secondary	Incidence of Renal Replacement Therapy at Month 6 and Month 12	Incidence of renal replacement therapy at Month 6 and Month 12: There were no incidences in either group where renal replacement therapy was required	Month 6, Month 12
Secondary	Time to Renal Replacement Therapy at Month 6 and Month 12	Time to renal replacement therapy at Month 6 and Month 12: There were no incidences in either group where renal replacement therapy was required	Month 6, Month 12
Secondary	Incidence of Acute Rejection Episodes at Month 6 and Month 12	Incidence of acute rejection episodes at Month 6 and Month 12. This table counts multiple occurrences of rejection in the same patient as different incidents. Every incident is associated with both an A and a B classification.; Classification A: Acute Rejection Grade 0 - none, Grade 1-minimal, Grade 2- mild, Grade 3-moderate, Grade 4-Severe; Classification B: Airway Inflammation-Grade 0-none, Grade 1R-low grade, Grade 2R-high grade, Grade X-ungradeable	Month 6, Month 12
Secondary	Incidence of Graft Loss/Re-transplantation at Month 6 and Month 12	Incidence of graft loss/re-transplantation at Month 6 and Month 12	Month 6, Month 12
Secondary	Incidence of Bronchiolitis Obliterans Syndrome (BOS) at Month 6 and Month 12	Incidence of Bronchiolitis obliterans syndrome (BOS) at Month 6 and Month 12 BOS 0 is FEV1 > 90% of baseline and FEF25-75% > 75% of baseline; BOS 0-p is FEV1 81-90% of baseline and/or FEF25-75% = 75% of baseline; BOS 1 is FEV1 66-80% of baseline; BOS 2 is FEV1 51-65% of baseline; BOS 3 is FEV1 = 50% of baseline	Month 6, Month 12
Secondary	Incidence of Death at Month 6 and Month 12	Incidence of death at Month 6 and Month 12	Month 6, Month 12
Secondary	Quality of Life (QoL, SF36) at Month 6 and Month 12	Quality of Life (QoL, SF36) at Month 6 and Month 12 Scores can range from a minimum of 0 (maximum disability) to a maximum of 100 (no disability).	Month 6, Month 12
Secondary	Exercise Capacity 6-Minute Walk Test(6MWT) at Month 6 and Month 12	Exercise capacity (6MWT) at Month 6 and Month 12 Measured by the Borg Scale. THE BORG SCALE 0 is Nothing at all, 0.5 is Very, very slight (just noticeable); 1 is Very slight, 2 is Slight (light); 3 is Moderate; 4 is Somewhat severe; 5 is Severe (heavy), 7 is Very severe, 10 is Very, very severe (maximal)The higher the Borg score implies increased shortness of breath and/or increased fatigue.	Month 6, Month 12
Secondary	Incidence of Treated Arterial Hypertension up to Month 12	Incidence of treated of arterial hypertension up to Month 12	up to Month 12
Secondary	Incidence of Diabetes Mellitus up to Month 12	Incidence of Diabetes Mellitus up to Month 12	up to Month 12
Secondary	Trough Levels of Everolimus at Month 1, 3, 6, 9, 12	Trough levels of everolimus at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	Adherence to Target Ranges of Everolimus at Month 1, 3, 6, 9, 12	Adherence to target ranges of everolimus at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	Trough Levels of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12	Trough levels of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	Adherence to Target Ranges of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12	Adherence to target ranges of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	Trough Levels of Tacrolimus at Month 1, 3, 6, 9, 12	Trough levels of Tacrolimus at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	Adherence to Target Ranges of Tacrolimus at Month 1, 3, 6, 9, 12	Adherence to target ranges of Tacrolimus at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	Incidence of Bacterial, Viral, and Fungal Infections at Month 12	Incidence of bacterial, viral, and fungal infections at Month 12	Month 12
Secondary	Triglyceride Levels at Month 1, 3, 6, 9, 12	Triglyceride levels at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	Total Cholesterol Levels at Month 1, 3, 6, 9, 12	Total Cholesterol levels at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	Low-Density Lipoprotein (LDL)Cholesterol Levels at Month 1, 3, 6, 9, 12	LDL Cholesterol levels at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12
Secondary	High-Density Lipoprotein (HDL)Cholesterol Levels at Month 1, 3, 6, 9, 12	HDL Cholesterol levels at Month 1, 3, 6, 9, 12	Month 1, 3, 6, 9, 12